An HSV‐1 Vector Expressing Tyrosine Hydroxylase Causes Production and Release of l‐DOPA from Cultured Rat Striatal Cells

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Abstract
In this report we demonstrate that a defective herpes simplex virus type one (HSV‐1) vector can express enzymatically active tyrosine hydroxylase in cultured striatal cells that are thereby converted into l ‐DOPA‐producing cells. A human tyrosine hydroxylase cDNA (form II) was inserted into an HSV‐1 vector (pHSVth) and packaged into virus particles using an HSV‐1 strain 17 mutant in the immediate early 3 gene (either ts K or D30EBA) as helper virus. Cultured fibroblasts were infected with pHSVth and 1 day later tyrosine hydroxylase immunoreactivity and tyrosine hydroxylase enzyme activity were observed. The tyrosine hydroxylase enzyme activity directed the production of l ‐DOPA. pHSVth infection of striatal cells in dissociated cell culture resulted in expression of tyrosine hydroxylase RNA and tyrosine hydroxylase immunoreactivity. Release of l ‐DOPA and low levels of dopamine were observed from cells in pHSVth‐infected striatal cultures. Expression of tyrosine hydroxylase and release of catecholamines were maintained for at least 1 week after infection.

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